Germicide



Patented July 30, 1940 UNlT ED STATES PATENT "o -"Flosoaarncma William H. Engels and John Weijlai'd, Railway. N. 1., assignors to Merck & Co. Inc., Rahway, N. J., a corporation of New Jersey No Drawing. Application April 9,1935, -Serial No. 15,426

7 Claims. (01. 167-532) g of the well-known insecticidal properties of 'rotenone,-one of the active constituents of Derris elliptica and of certain South American plants, it has been suggested for use in treating h diseases of thetype under discussion. It has been shown by the work of Sonkichi 'Iakei, U. S.

Patent #l,724,626, that rotenone, as such, or as present in derris extract is itself unstable in the presence of water and alkali, which accounts for the instability and unsatisfactory character, of ordinary preparations made up, for instance,

- with industrial alcohol and soap powders.

The direct use of solutions of rotenone in absolute alcohol, acetone, or other similar volatile organic solvents, in whichthis principle is fully soluble, are nevertheless ineifective for the purpose under consideration because when such a solution is applied, the warmth of the animals body causes the solvent to evaporate rapidly, 20 leaving the rotenone on the surface of the af-f fected parts. The medicament is thus prevented from reaching the parasitic organisms which thrive in the skin at the roots of the hair.

, We'havenow found it possible to produce satcs isfactory preparations utilizing pure rotenone itself, or extracts of rotenone-bearing plants (such as Derris elliptica and barbasco or barbasco cube) which overcome these' objections, by dissolving the remedial agent in suitable solvents 3 of the type mentioned above, and then combiningthem with emollient and skin-penetrating carrying agents.

This invention relates to certain preparations fo'rthe treatment of parasitic skin diseases, and

' 85 morepa'rticularly for-the treatment of such diseases in animals.

- Animals, and especially dogs, are peculiarly susceptible to the disease commonly known as red mange, a disease resulting from the invasion of the hair follicles by the parasite Demodez jollicizlorum. .For the treatment of this. disease,

many remedies have been advanced. However,

none of these has' been entirely satisfactory;

45 chiefly because the agencies employed act too slowly or because the forms in which they are administered are not sumciently penetrating to combat the ravages of the parasite.

7 Such preparations are made by first dissolving 50 the rotenone or extract in relatively'non-irritating volatile solvents such as acetone, benzene, absolute alcohoL-chloroform, etc., and admixing the solutions thus obtained with vegetable or animal-fatty oils, such as olive oil, peanut oil,

e: neats-foot oil, etc., or with fats of the type of anhydrous wool fat for thepreparation of the remedy in ointment formr therefore, the preferred employment of the active principle has been preferably restricted to, use in the form of extracts of the derris species. We have now found that in our new method of preparing these products we can utilizepure v rotenone itself as well as rotenone-containing 2 plant extracts, such as derris extract, with equal advantage. Obviously, the use of pure rotenone, per se, has the advantage ,of more definite quantitative control and dosage, although the other preparations may be economically preferable-'25 .In preparing an effective stabilized product containing rotenone, in accordance with this invention, we employ non-aqueous volatile solvents which are non-toxic when used externally, and

which very readily and thoroughly dissolve the 3 medicament. The volatile pre-solvents selected are also soluble in animal or vegetable fatty oils orfats, and serve as preservatives for the, oil solutions which are subsequently prepared. The pre-solution in the volatile solvents and the subsequent solution in fatty oils or fats produce; compounds which, when applied to diseased surfaces, lend themselves to even distribution of the medicament over the afiected areas. Furthermore, these oils or fats, in addition to their func- 40 tion as stabilizing carriers, serve also as emollients and thus tend to counteract any irritating 61' drying effects of the volatile solvents upon the skin ,of the animal being "treated, and, because of theiramnity to skin tissue, penetrate it deeply and thus carry the active principle to the diseased tissue in sufliciently efiective quantities for the purpose of attacking and destroyingjthe par-1 Rotenone in the form of derris extract has hitherto been employed as an insecticide (largeli for agricultural purposes) generally in the-Iona; a

of a dry dusting powder or extemporan'eously prepared solutions.

Owing to the recognized instabilityof the ma- .An'oilsolution or ointment as described, con

taining as little as ti of 1% or as much as 2% or even more pure rotenone (or derris or other rotenone-bearing extract), may be'uniiormly ap-" plied to the afl'ected areas by any appropriate means without toxic effect, and has been found to exert beneficial action on the diseased areas in a relatively short time, as is usually evidence by early cessation of the severe itching which is one 01' the characteristics of the disease, and by anabundant growth of new fur. I

In cases where the disease has progressed to an advanced stage and secondary infection by bacteria has set in, it will often be avisable to add also an oil-soluble germicide oi the class of cresols, xylenols, and other phenol homologs, with or without halogen groups in the molecule such as thymol, chlorthymol, dichlorhexylphenol etc. Such adjuvant substances may be added to our stabilized rotenone compounds without danger of impairing the parasiticidal properties 01 the rotenone or derris component., r

The products described herein may be prepared by the following methods:

(1) One pound of derris extract is dissolved in 10 pints of acetone and to this solution is added 90 pints of olive oil; (2) To a solution oil lb. pure rotenone in 5 pints benzene, are added 95 pints of peanut oil; (3) One-half lb. of derris extract is dissolved in 5 pints of chloroform and the solution added to 95 pints of peanut oil; (4) Two pounds .0! derris extract and one pound chlorthymol are dissolved in 5'pints of chloroform and,the solution added to 95 pounds of anhydrous wool fat; one pound of rotenone is added to about ten pints of chloroform and the solution added to about 90 pints of olive oil; one pound of crude derris extract is added to ten pints of acetone, and the solution added to ninety pints of peanut oil; a halt pound of pure rotenone is dissolved in'flve pints of absolute alcohol, and the solution added to ninety-five pints of olive oil and one pound of fled above. It is to be, understood, of course, that these methods are given by way of illustration only and that they represent materials which may be prepared by pre-solution o! the active principle in solvents comprising preferably volatile liquids of the type described and subsequent solution in.-a wide range of bland animal or vegetable fatty oils or tats.

pints of oliveoil and a pound of chlorthymol.

In general, it is desirable that the amount of non-aqueous solvent employed for predissolving and dispersing the rotenone, respectively, rotenone-bearing extract in the emollient oil or fat employed as stable carrying agent, should be held to a relatively small quantity, yet suillcient to incorporated. H y

We claim as our invention:

1. A composition of matter comprising a sub- 's tance selected from the group consisting .of

rotenone and rotenone-bearing extracts, a substance selected Irom the group consisting of emollient vegetableand animal fats and oils. and a non-toxic, non-aqueous volatile solvent the rotenone being present in suiflcient quantity to eflectively destroy Demodez: folliculorum, and the volatile solvent, being present in a quantity sufllcient to dissolve the rotenone and stabilizethe mixture, but insumcient to harmiully eflect the skin of a hirsute animal.

2. A, stabilized rotenone preparation for the treatment of parasitic skin diseases which com-' prises a rotenone-bearing plant-extract, a nontoxic, non-aqueous, volatile solvent, and a subemollient animal and vegetable fatty oils and fats, said rotenone being present in sufllcient quantity that upon repeated application it eflec stance selected from the group consisting of emollient animal and vegetable oils and fats, and a non toxic, non-aqueous volatile solvent present in a quantity sumcient to dissolve the rotenone and stabilize the-mixture, but insufllcient to harmiully eflect the skin of a hirsute animal. 4. A preparation for the treatment of parasitic skin diseases which consists of barbasco extract,

a substance selected from the group consistingof emollient animal and vegetable oils and fats, and a non-toxic, non-aqueous volatile solvent present in a quantity suillcient to dissolve the barbasco extract and stabilize the mixture but insumcient to harmiully eiliect the skin of a hirsute animal.

5. A stable solution comprising one pound of pure rotenone, 10 pints of cholorformand pints of olive oil. v 6. A stable solution comprising one pound of crude derris extract, 10 pints of acetone, and 90 pins 01' peanut oil.

7. A stable solution comprising pound oi pure rotenone, 5 pints of absolute alcohol,

wnlusmin. Enema. some wnmnn stance selected from the group -consisting oi as 

